Kentaro Yokoi

Allogenic bone marrow transplantation for late-infantile neuronal ceroid lipofuscinosis

Late-infantile neuronal ceroid lipofuscinosis (NCL2; 204500) is a rare progressive neurodegenerative disorder with an autosomal recessive inheritance. NCL2 shows progressive myoclonic epilepsy and neurological deterioration with an onset usually between 2 and 4 years of age. The progressive loss of neurological function leads to premature death in the first or second decade of life. The gene responsible for classic NCL2, CLN2 , has been mapped to 11p15 1 and deficiency of CLN2 gene product, tripeptidyl peptidase-1 (TPP-1; E.C. 3.4.14.9), is considered to be the cause of this disease. 2–4 However, there are at least three other genetic variations within NCL2. Biochemically, NCL2 is divided into two categories based on the presence of TPP-1 activity. Currently there are no direct therapies other than supportive therapies reported. Bone marrow transplantation (BMT) as therapy has been previously reported. 5,6 Although there was engraftment failure, they reported retarded disease progression.

Multidisciplinary therapy including proton beam radiotherapy for a Ewing sarcoma family tumor of maxillary sinus in a 4-year-old girl

Although complete resection offers the best chance for controlling head and neck Ewing sarcoma family tumors (ESFTs), it is occasionally unfeasible because of possible functional and cosmetic side effects. Planning multidisciplinary treatment for head and neck ESFT is challenging.

Rapid spontaneous regression of multicentric infantile myofibromatosis in the posterior fossa and lumbar vertebra

Infantile myofibromatosis is the most common fibrous tumor of infancy and early childhood. It typically occurs in skin, subcutaneous tissue, muscle, bone, and/or viscera. In patients without visceral involvement, the prognosis is excellent, generally with spontaneous regression of the tumor nodules in 1 to 2 years [1]. However, they show unfavorable prognosis within the first few months of life if there is visceral involvement [1]. Intracranial involvement is rare, and to our knowledge, only 17 such cases have been reported [1–15]. Although lesions usually arise from the dura [16] and grow in one direction, either epidural or subdural, in our case, there was equal growth epidurally and subdurally. Spontaneous regression occurred at the same time as that of a lumbar lesion 3 months after biopsy. This unique course has never been reported, and the rate of regression in this case was remarkable. Case report

Severe aplastic anaemia complicating Sjögren syndrome in a 2-year-old girl.

We report a 2.5-year-old Japanese girl with severe aplastic anaemia complicating Sjögren syndrome. The patient had been born at 39 weeks’ gestation via an uncomplicated vaginal delivery as the first child of non-consanguineous parents. Birth weight was 2865 g (-0.58 SD), length was 48.3 cm (-0.31 SD), and occipitofrontal circumference was 32.0 cm (-0.84 SD). A developmental delay in gross motor performance had been noted at 10 months of age; however, she could assume a sitting position at the age of 18 months and could walk well at the age of 27 months. At the age of 21 months, a CT scan showed intracranial calcifications bilaterally in the basal ganglia and the deep cortical white matter. Moreover, laboratory studies showed anaemia (haemoglobin 8.4 g/dl) and liver dysfunction (aspartate aminotransferase 102 IU/dl, and alanine aminotransferase 83 IU/dl). Immunoglobulin (Ig)G and IgM antibodies against cytomegalovirus (CMV) were positive and negative, respectively; however, CMV was not isolated from the peripheral blood, urine, or CSF. She had routinely been brought to us because of a developmental delay due to suspected congenital CMV infection. Her family history was remarkable for a maternal grandmother with Sjögren syndrome complicating idiopathic thrombocytopenic purpura. At the age of 30 months, the patient was admitted to our hospital because of febrile convulsions. Her mother noted that she had been pale with purpura on both legs for 1 month. Physical examination on admission showed no anomalies such as short stature, nail dystrophy, and bone or urogenital tract malformations. In addition, there was no rash, leukoplakia, or hyperpigmentation in the skin. Haematological investigations unexpectedly showed anaemia (haemoglobin 9.0 g/dl) and thrombocytopenia (platelet count, 1.6·10/ll). Bone marrow examination revealed hypocellularity (17·10/ll) without megakaryocytes or proliferation of blasts, leading to a diagnosis of aplastic anaemia. Analysis of surface markers of bone marrow cells with flow cytometry revealed the following: CD2 70.8%; CD3 66.8%; CD4 37.9%; CD5 70.7%; CD7 67.8%; CD8 29.8%; CD13 9.3%; CD14 6.3%; CD33 12.8%; and CD34 3.6%. At the age of 34 months, haematological studies showed severe aplastic anaemia; haemoglobin 5.6 g/dl; haematocrit 14.9%; red blood cell count 190·10/ll; reticulocyte count 1.9·10/ll; platelet count 1.7·10/ll; white blood cell count 3400/ll; and granulocyte count 34/ll. Bone marrow biopsy revealed markedly hypoplastic marrow (nucleated cell count 11·10/ll) consisting chiefly of fat and fibrous tissue, and lymphocytes without immature or differentiated myeloid cells or megakaryocytes (Fig. 1). There was no chromosomal abnormality. Analysis of surface markers with flow cytometry revealed increased numbers of bone marrow T-cells (CD2 89.0%; CD3 83.5%; CD4 40.6%; CD5 89.4%; CD7 87.3%; CD8 40.7%), and decreased numbers of myeloid cells (CD13 4.7%; CD14 1.9%; CD33 3.3%) and haematopoietic stem cells (CD34 1.5%), compared with investigations performed at the age of 30 months. Severe anaemia and thrombocytopenia necessitated transfusions of erythrocytes and platelets every week. However, treatment with granulocyte colonystimulating factor did not increase the granulocyte count. Pyrexia and bilateral parotid gland enlargement (Fig. 2A) had been noted twice, at the age of 33 and 36 months. Immunological examination showed high serum levels of IgG (2,042 mg/dl) and IgE (1,899 mg/dl) and low CH50 activity (6.2 U/ml). In addition, M. Akiyama (&) Æ T. Yanagisawa Æ Y. Yuza Æ K. Yokoi K. Fujisawa Æ S. Kobayashi Æ Y. Eto Department of Paediatrics, Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, 105-8461 Tokyo, Japan E-mail: makiyama@jikei.ac.jp Tel.: +81-3-34331111 Fax: +81-3-34358665

Hemoglobin Hammersmith [β 42(CD1) Phe → Ser] causing severe hemolytic anemia in a Japanese girl

Hemoglobin Hammersmith, a rare, unstable hemoglobin variant, was diagnosed in a 9‐year‐old Japanese girl. She presented with the typical manifestations of this disorder, including neonatal hyperbilirubinemia, followed by progressive hepatosplenomegaly, jaundice, and bilirubinuria. Because of severe hemolytic anemia, she received transfusions of red blood cells every 3 to 4 weeks. However, she underwent splenectomy at the age of 4 years and has continued to be in partial remission without requiring further transfusions. DNA sequence analysis of the polymerase chain reaction‐amplified β‐globin gene revealed a point mutation (T → C) in the second nucleotide of the 42nd codon of the β‐globin chain (β 42(CD1) Phe → Ser). Pediatric Blood Cancer 2006;47:839–841.

Differences in CTG triplet repeat expansion in leukemic cells and normal lymphocytes from a 14-year-old female with congenital myotonic dystrophy

We describe a rare case of acute lymphoblastic leukemia in a 14‐year‐old female with congenital myotonic dystrophy manifested as mental retardation, extensive contractures of multiple joints of the lower extremities, and severe scoliosis. Because of the potential toxicity of chemotherapy and the patients poor performance status, a modified chemotherapy regimen was administered. Analysis of the greatly expanded number of CTG repeats at the 3′ untranslated region of DMPK gene showed that the number of repeats was 233 greater in leukemic cells than in normal lymphocytes; this elongation may have occurred during the cellular proliferation of leukemic clones. Pediatr Blood Cancer 2008;51:563–565.

Paraneoplastic Syndrome of Angiomatoid Fibrous Histiocytoma May Be Caused by EWSR1-CREB1 Fusion-induced Excessive Interleukin-6 Production.

We describe a 7-year-old girl with angiomatoid fibrous histiocytoma (AFH) presenting severe inflammatory symptoms. The cytokine/chemokine profile of serum samples before and after surgery demonstrated that interleukin (IL)-6 had decreased by the greatest percentage. The AFH cells were immunopathologically positive for IL-6 and Tyr705-phosphorylation of signal transducer and activator of transcription 3. The EWSR1-CREB1 fusion gene detected in the tumor leads to continuous activation of CREB1 and IL-6 production, because the promoter region of IL-6 has a CREB binding site. Thus, IL-6 plays pivotal roles in both paraneoplastic syndrome and the oncogenesis of AFH.

Sequential analysis of cadherin expression in a 4-year-old girl with intracranial ependymoma

IntroductionCadherins are Ca2+-dependent cell-to-cell adhesion molecules that play an important role in tissue construction and morphogenesis in multicellular organisms. Cadherin involvement in tumor metastasis has recently been reported.Case reportWe investigated the expression of E-cadherin and N-cadherin in paraffin-embedded sequential surgical specimens and autopsy specimens from a 4-year-old girl with recurrent ependymoma, subsequent to cerebrospinal fluid (CSF) dissemination. We observed low expression of E-cadherin in all surgical specimens and autopsy specimens. In contrast, expression of N-cadherin was high in all surgical specimens, but was decreased in autopsy specimens.ConclusionDecreased expression of N-cadherin may be associated with CSF dissemination and may serve as a useful marker for CSF dissemination in patients with intracranial ependymoma.

RNA expression analysis of a congenital intracranial teratoma

Congenital intracranial tumors are extremely rare and account only for 0.5%–1.5% of brain tumors in children. We report a large intrauterine congenital teratoma in a female fetus at gestation weeks 37, which was diagnosed by detecting the tumor and associated craniomegaly with ultrasonography (US) and magnetic resonance (MR) imaging. The tumor had replaced the cerebral hemispheres and produced prenatal manifestations. Pathologic examination showed an immature teratoma, which was differentiated from all three germ layers. Microarray analysis revealed upregulation of ten genes and downregulation of three genes, as well as upregulation of 41 genes of ribosomal proteins in teratoma cells, compared to normal brain tissue of the patient. The data from the microarray analysis offer not only the potential to help define disease pathogenesis but may also provide clues to identify potential molecular therapeutic targets.

Atypical clinical features of children with central nervous system tumor: Delayed diagnosis and switch in handedness.

Herein is described the cases of three children with central nervous system (CNS) tumor, who had switch in handedness occurring before diagnostic confirmation. Although the onset, age, tumor location, and histology were heterogeneous, the diagnosis of CNS tumor was delayed in all three patients. The present experience indicates that switch in handedness should be recognized as a sign of CNS tumor in pediatric patients, and which might prevent delay in diagnosis. Pediatricians should carefully examine such patients who present with some suggestive symptoms of CNS tumor, even when they are unusual, in order to make a timely and appropriate diagnosis.